Music-listening regulates human microRNA expression.

Music-listening and performance have been shown to affect human gene expression. In order to further elucidate the biological basis of the effects of music on the human body, we studied the effects of music-listening on gene regulation by sequencing microRNAs of the listeners (Music Group) and their controls (Control Group) without music exposure. We identified upregulation of six microRNAs (hsa-miR-132-3p, hsa-miR-361-5p, hsa-miR-421, hsa-miR-23a-3p, hsa-miR-23b-3p, hsa-miR-25-3p) and downregulation of two microRNAs (hsa-miR-378a-3p, hsa-miR-16-2-3p) in Music Group with high musical aptitude. Some upregulated microRNAs were reported to be responsive to neuronal activity (miR-132, miR-23a, miR-23b) and modulators of neuronal plasticity, CNS myelination, and cognitive functions like long-term potentiation and memory. miR-132 plays a critical role in regulating TAU protein levels and is important for preventing tau protein aggregation that causes Alzheimer's disease. miR-132 and DICER, upregulated after music-listening, protect dopaminergic neurons and are important for retaining striatal dopamine levels. Some of the transcriptional regulators (FOS, CREB1, JUN, EGR1, and BDNF) of the upregulated microRNAs were immediate early genes and top candidates associated with musical traits. BDNF and SNCA, co-expressed and upregulated in music-listening and music-performance, are both are activated by GATA2, which is associated with musical aptitude. Several miRNAs were associated with song-learning, singing, and seasonal plasticity networks in songbirds. We did not detect any significant changes in microRNA expressions associated with music education or low musical aptitude. Our data thereby show the importance of inherent musical aptitude for music appreciation and for eliciting the human microRNA response to music-listening.

Music-performance regulates microRNAs in professional musicians.

Musical training and performance require precise integration of multisensory and motor centres of the human brain and can be regarded as an epigenetic modifier of brain functions. Numerous studies have identified structural and functional differences between the brains of musicians and non-musicians and superior cognitive functions in musicians. Recently, music-listening and performance has also been shown to affect the regulation of several genes, many of which were identified in songbird singing. MicroRNAs affect gene regulation and studying their expression may give new insights into the epigenetic effect of music. Here, we studied the effect of 2 hours of classical music-performance on the peripheral blood microRNA expressions in professional musicians with respect to a control activity without music for the same duration. As detecting transcriptomic changes in the functional human brain remains a challenge for geneticists, we used peripheral blood to study music-performance induced microRNA changes and interpreted the results in terms of potential effects on brain function, based on the current knowledge about the microRNA function in blood and brain. We identified significant (FDR <0.05) up-regulation of five microRNAs; hsa-miR-3909, hsa-miR-30d-5p, hsa-miR-92a-3p, hsa-miR-222-3p and hsa-miR-30a-5p; and down-regulation of two microRNAs; hsa-miR-6803-3p and hsa-miR-1249-3p. hsa-miR-222-3p and hsa-miR-92a-3p putatively target FOXP2, which was found down-regulated by microRNA regulation in songbird singing. miR-30d and miR-222 corroborate microRNA response observed in zebra finch song-listening/learning. miR-222 is induced by ERK cascade, which is important for memory formation, motor neuron functions and neuronal plasticity. miR-222 is also activated by FOSL1, an immediate early gene from the FOS family of transcriptional regulators which are activated by auditory-motor stimuli. miR-222 and miR-92 promote neurite outgrowth by negatively regulating the neuronal growth inhibitor, PTEN, and by activating CREB expression and phosphorylation. The up-regulation of microRNAs previously found to be regulators of auditory and nervous system functions (miR-30d, miR-92a and miR-222) is indicative of the sensory perception processes associated with music-performance. Akt signalling pathway which has roles in cell survival, cell differentiation, activation of CREB signalling and dopamine transmission was one of the functions regulated by the up-regulated microRNAs; in accordance with functions identified from songbird learning. The up-regulated microRNAs were also found to be regulators of apoptosis, suggesting repression of apoptotic mechanisms in connection with music-performance. Furthermore, comparative analyses of the target genes of differentially expressed microRNAs with that of the song-responsive microRNAs in songbirds suggest convergent regulatory mechanisms underlying auditory perception.